一种血清素能轴突-纤毛突触驱动核信号转导改变染色质可及性。
A serotonergic axon-cilium synapse drives nuclear signaling to alter chromatin accessibility.
机构信息
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; Harvard Medical School, Boston, MA, USA; Boston Children's Hospital, Department of Pathology, Boston, MA, USA; Howard Huges Medical Institute, Boston Children's Hospital, Department of Cardiology, Boston, MA, USA.
Advanced Bioimaging Center, University of California at Berkeley, Berkeley, CA, USA; Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA.
出版信息
Cell. 2022 Sep 1;185(18):3390-3407.e18. doi: 10.1016/j.cell.2022.07.026.
Chemical synapses between axons and dendrites mediate neuronal intercellular communication. Here, we describe a synapse between axons and primary cilia: the axo-ciliary synapse. Using enhanced focused ion beam-scanning electron microscopy on samples with optimally preserved ultrastructure, we discovered synapses between brainstem serotonergic axons and the primary cilia of hippocampal CA1 pyramidal neurons. Functionally, these cilia are enriched in a ciliary-restricted serotonin receptor, the 5-hydroxytryptamine receptor 6 (5-HTR6). Using a cilia-targeted serotonin sensor, we show that opto- and chemogenetic stimulation of serotonergic axons releases serotonin onto cilia. Ciliary 5-HTR6 stimulation activates a non-canonical G-RhoA pathway, which modulates nuclear actin and increases histone acetylation and chromatin accessibility. Ablation of this pathway reduces chromatin accessibility in CA1 pyramidal neurons. As a signaling apparatus with proximity to the nucleus, axo-ciliary synapses short circuit neurotransmission to alter the postsynaptic neuron's epigenetic state.
轴突和树突之间的化学突触介导神经元细胞间通讯。在这里，我们描述了轴突和初级纤毛之间的突触：轴突-纤毛突触。通过对具有最佳超微结构保存的样本进行增强的聚焦离子束扫描电子显微镜检查，我们发现了脑干 5-羟色胺能轴突和海马 CA1 锥体神经元的初级纤毛之间的突触。功能上，这些纤毛富含一种纤毛受限的 5-羟色胺受体，即 5-羟色胺受体 6（5-HTR6）。使用纤毛靶向 5-羟色胺传感器，我们表明光遗传学和化学遗传学刺激 5-羟色胺能轴突可将 5-羟色胺释放到纤毛上。纤毛 5-HTR6 刺激激活非经典的 G-RhoA 途径，该途径调节核中的肌动蛋白并增加组蛋白乙酰化和染色质可及性。该途径的缺失会降低 CA1 锥体神经元中的染色质可及性。作为一种与核接近的信号装置，轴突-纤毛突触将神经传递短路，改变突触后神经元的表观遗传状态。
Zotero 插件